PROJECT SUMMARY Axonal injuries, such as spinal cord injury, are common health issues. To find a way to cure axonal injuries we need to know the mechanisms of axon regeneration. My previous studies showed that regulation of cebp-1 mRNA stabilization and local protein translation by the DLK-1 pathway is required for successfully axon regeneration. However, how axonal injury activates the DLK signaling pathway, how DLK-1 regulates multiple downstream pathways, and what are CEBP-1 downstream targets are still unclear. In this study, I propose experiments to address these questions. Ultimately, I want to find a way to modulate the DLK-1 pathway to promote functional recovery after axonal injury in C .elegans and the mouse. The emphasis in the mentored phase of the award will be on the activation mechanisms of DLK-1 and uncovering DLK-1 negatively regulated genes. In the independent phase, I will further study the regulatory mechanisms of DLK-1 negatively regulated genes, and systematically analyze CEBP-1 transcriptional targets and axonal functions.